The vascular tumors significantly dropped in volume, redness, and elevation from the skin with a six-month course of propranolol compared with placebo, found Marcia Hogeling, MD, and colleagues at Sydney Children's Hospital in Australia.
The drug also appeared safe with no significant hypertension, hypoglycemia, or bradycardia among the cohort of 40 children, up to five-years-old, the group reported in the August issue of Pediatrics.
The dramatic responses seen with propranolol could mean that early treatment would reduce scarring and disfigurement, Hogeling and colleagues suggested.
Despite the small sample size, these results may be "sufficient to justify the use of propranolol as the first-line option for potentially disfiguring or complicated" cases, they argued in the paper.
Many physicians, though, have already adopted this strategy based on positive results from case series, the group noted.
Patients often don't get referred for treatment soon enough to benefit from the antiproliferative effect of systemic corticosteroids, the gold standard for treatment. And a response to treatment does not consistently occur in those who do receive corticosteroids, they explained.
Large clinical trials using propranolol for infantile hemangiomas are underway. For an early look at efficacy and safety, Hogeling's group randomized 40 children, ages 11 weeks to 5 years, to a six month course of 2 mg/kg of oral propranolol or placebo divided into three doses each day.
All the children had infantile hemangiomas deep under the skin, or located in sites such as the tip of the nose or around the eye, which could impair function or be disfiguring. The patient had either presented too late for corticosteroid therapy or had not responded to therapy.
For the primary endpoint, propranolol-treated growths steadily shrank to reach an average 60% of their initial size at 24 months.
Placebo-treated tumors grew for the first half of the study period then shrank for a final 14.1% volume reduction at 24 months, a difference that was substantially and significant different than active treatment at P=0.01.
Redness and elevation of the tumors also decreased significantly more with propranolol (both P=0.01 at 24 months).
Blueness of the hemangiomas didn't differ between groups, although relatively few children in the study presented early enough for blueness to be seen in the proliferative stage of tumor growth, the researchers noted.
Adverse events with propranolol included:
- Four cases of bronchiolitis compared with one in the placebo group
- One case of upper respiratory tract infection versus none in the placebo group
- Two cases in each group of sleep disturbance with crying episodes, which the researchers noted were possibly due to nightmares
- One case each of cold hands or feet, streptococcal infection, viral gastroenteritis, elevated alkaline phosphatase, and dental cavities compared with none in the placebo group
- One case of infantile hemangioma ulceration in each group
Though not formally evaluated in the study, rebound growth of the tumors was noted when propranolol dosing stopped, particularly in children younger than 1 year.
Further studies are needed to determine the optimal duration of treatment, the researchers noted.
They cautioned that the range of ages recruited into their trial may have made it difficult to distinguish partial response to the drug from the natural involution that often occurs with infantile hemangiomas as children get older.
Not all children responded dramatically, but all did have some shrinkage.
"The medication may be particularly useful in this group to hasten involution as a replacement to early surgery or to lower the age at which timely surgery can be performed to maximize excision with minimal scarring," Hogeling's group concluded.
The study was funded by the Sydney Children's Hospital Foundation, Pediatric Cardiac Fund, and the Touched by Olivia Foundation.
The researchers reported having no conflicts of interest to disclose.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner